Centromere-Specific Assembly of CENP-A Nucleosomes Is Mediated by HJURP

Daniel R. Foltz; Lars E T Jansen; Aaron O. Bailey; John R. Yates; Emily A. Bassett; Stacey Wood; Ben E. Black; Don W. Cleveland

doi:10.1016/j.cell.2009.02.039

Centromere-Specific Assembly of CENP-A Nucleosomes Is Mediated by HJURP

Daniel R. Foltz^*, Lars E T Jansen, Aaron O. Bailey, John R. Yates, Emily A. Bassett, Stacey Wood, Ben E. Black, Don W. Cleveland

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

522 Scopus citations

Abstract

The centromere is responsible for accurate chromosome segregation. Mammalian centromeres are specified epigenetically, with all active centromeres containing centromere-specific chromatin in which CENP-A replaces histone H3 within the nucleosome. The proteins responsible for assembly of human CENP-A into centromeric nucleosomes during the G1 phase of the cell cycle are shown here to be distinct from the chromatin assembly factors previously shown to load other histone H3 variants. Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.

Original language	English (US)
Pages (from-to)	472-484
Number of pages	13
Journal	Cell
Volume	137
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2009.02.039
State	Published - May 1 2009

Keywords

CELLBIO
CELLCYLE

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2009.02.039

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@article{7469e8e8b24a4526a786d06a6c93d374,

title = "Centromere-Specific Assembly of CENP-A Nucleosomes Is Mediated by HJURP",

abstract = "The centromere is responsible for accurate chromosome segregation. Mammalian centromeres are specified epigenetically, with all active centromeres containing centromere-specific chromatin in which CENP-A replaces histone H3 within the nucleosome. The proteins responsible for assembly of human CENP-A into centromeric nucleosomes during the G1 phase of the cell cycle are shown here to be distinct from the chromatin assembly factors previously shown to load other histone H3 variants. Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.",

keywords = "CELLBIO, CELLCYLE",

author = "Foltz, {Daniel R.} and Jansen, {Lars E T} and Bailey, {Aaron O.} and Yates, {John R.} and Bassett, {Emily A.} and Stacey Wood and Black, {Ben E.} and Cleveland, {Don W.}",

note = "Funding Information: The authors thank Iain Cheeseman, Andrew Holland, Karen Oegema, Arshad Desai, and members of the Cleveland Lab for helpful discussion and reagents. This work was supported by grants from the National Institutes of Health to B.E.B. and D.W.C. D.R.F. was supported by a Special Fellowship from the Leukemia and Lymphoma Society. B.E.B. was supported by a Career Award in the Biomedical Sciences from the Burroughs Welcome Fund. L.E.T.J. was supported by a postdoctoral fellowship from Philip Morris USA Inc. Salary support for D.W.C. is provided by the Ludwig Institute for Cancer Research. ",

year = "2009",

month = may,

day = "1",

doi = "10.1016/j.cell.2009.02.039",

language = "English (US)",

volume = "137",

pages = "472--484",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

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T1 - Centromere-Specific Assembly of CENP-A Nucleosomes Is Mediated by HJURP

AU - Foltz, Daniel R.

AU - Jansen, Lars E T

AU - Bailey, Aaron O.

AU - Yates, John R.

AU - Bassett, Emily A.

AU - Wood, Stacey

AU - Black, Ben E.

AU - Cleveland, Don W.

N1 - Funding Information: The authors thank Iain Cheeseman, Andrew Holland, Karen Oegema, Arshad Desai, and members of the Cleveland Lab for helpful discussion and reagents. This work was supported by grants from the National Institutes of Health to B.E.B. and D.W.C. D.R.F. was supported by a Special Fellowship from the Leukemia and Lymphoma Society. B.E.B. was supported by a Career Award in the Biomedical Sciences from the Burroughs Welcome Fund. L.E.T.J. was supported by a postdoctoral fellowship from Philip Morris USA Inc. Salary support for D.W.C. is provided by the Ludwig Institute for Cancer Research.

PY - 2009/5/1

Y1 - 2009/5/1

N2 - The centromere is responsible for accurate chromosome segregation. Mammalian centromeres are specified epigenetically, with all active centromeres containing centromere-specific chromatin in which CENP-A replaces histone H3 within the nucleosome. The proteins responsible for assembly of human CENP-A into centromeric nucleosomes during the G1 phase of the cell cycle are shown here to be distinct from the chromatin assembly factors previously shown to load other histone H3 variants. Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.

AB - The centromere is responsible for accurate chromosome segregation. Mammalian centromeres are specified epigenetically, with all active centromeres containing centromere-specific chromatin in which CENP-A replaces histone H3 within the nucleosome. The proteins responsible for assembly of human CENP-A into centromeric nucleosomes during the G1 phase of the cell cycle are shown here to be distinct from the chromatin assembly factors previously shown to load other histone H3 variants. Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.

KW - CELLBIO

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U2 - 10.1016/j.cell.2009.02.039

DO - 10.1016/j.cell.2009.02.039

M3 - Article

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AN - SCOPUS:65249115338

SN - 0092-8674

VL - 137

SP - 472

EP - 484

JO - Cell

JF - Cell

IS - 3

ER -

Centromere-Specific Assembly of CENP-A Nucleosomes Is Mediated by HJURP

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